In addition to healthy lifestyle behaviors including regular physical activity, abstaining from tobacco, healthy nutrition and optimal weight control, lipid lowering therapy remains the mainstay for effective prevention and management of atherosclerotic cardiovascular disease (ASCVD) (primarily coronary heart disease and cerebrovascular disease), the leading cause of mortality and morbidity in the United States.

What is atherosclerosis?

Atherosclerosis is the process of plaque build-up in arteries by atherogenic lipid particles that penetrate the arterial walls and promote inflammation, which over time results in arterial narrowing and restriction of blood flow to organs such as the heart or the brain, potentially causing heart attacks and strokes.

Why lower cholesterol, and why earlier?

The rationale for cholesterol-lowering therapy is grounded in decades of epidemiologic, genetic, imaging, and randomized clinical trial evidence demonstrating that ASCVD is driven largely by cumulative exposure to atherogenic lipoproteins, especially low-density lipoprotein cholesterol (LDL-C) (“bad” cholesterol). Evidence shows that ASCVD develops over decades before it is clinically evident and therefore a central theme of the new guidelines is to test lipids earlier (initial test recommended at age 9-11) and maintain desirable values throughout life. Clinical trials consistently show that lowering LDL-C reduces the risk of heart attack, stroke, and cardiovascular mortality, with benefit proportional to the magnitude and duration of LDL reduction; “lower and earlier is better”.

LDL targets

Under the new guidelines, LDL cholesterol level remains the main treatment target to follow, depending on individual risk:

A new way to estimate risk

A major change in the new guidelines is the use of the newer PREVENT risk calculator to estimate 10 and 30-year risk of heart attack or stroke. This calculator is based on age, gender, body mass index, systolic blood pressure, hypertension treatment, non-HDL cholesterol, “good” HDL, use of statin drugs, diabetes, smoking status and kidney function tests. Unfortunately, it still does not incorporate family history of ASCVD.

Beyond the basic lipid profile

The new guidelines broaden the focus from basic lipid profile and LDL to “dyslipidemia” including lipoprotein (a) (Lp(a)), recommended at least once in adult lifetime, and apolipoprotein B (ApoB).

Treatment

Statin therapy remains the proven cornerstone of lipid lowering therapy and improved ASCVD outcomes. If LDL target goal is not achieved by the maximally tolerated statin dose, combination therapy with other meds such as ezetimibe (Zetia), PCSK9 inhibitors (e.g. Repatha) and/or Bempedoic acid is recommended.

The bottom line

Overall, the 2026 guidelines represent a shift from reactive treatment of established disease towards proactive, lifelong-based prevention aimed at minimizing cumulative exposure to atherogenic lipoproteins. The central message is that aggressive early lipid lowering prevents ASCVD events more effectively than delayed intervention.